Complex atypical endometrial hyperplasia (CAH) carries a high probability of cancer. Intraoperative evaluation of endometrial cancer in cases of CAH has not been reliable. The safety and sensitivity of sentinel lymph node (SLN) sampling has been validated. We aim to evaluate the efficacy and safety of SLN sampling in CAH managed by the da Vinci robotic platform. A total of 113 patients with a preoperative diagnosis of CAH were included in this retrospective cohort study. All underwent a robot assisted total laparoscopic hysterectomy and bilateral salpingo-oophorectomy with 69 patients undergoing SLN sampling. Statistical analysis calculated the probability of cancer, SLN map rate, and surgical complications. Predictors of cancer were evaluated. Forty-seven percent of the entire cohort were diagnosed with endometrial cancer. Median age was 63 years in the SLN cohort (N = 69) and 61 in the No SLN cohort (N = 44) (p= 0.363).  Median BMI was 34 Kg/m2 in the SLN cohort and 40 in the No SLN cohort (p= 0.004). Bilateral SLN map was 92.8% and unilateral SLN map rate was 7.2%. There were no grade 3-4 complications in the SLN cohort, and 4 grade 3-4 complications in the No SLN group (p=0.021). A preoperative diagnosis of CAH bordering on or cannot rule out cancer was the only predictor of cancer.

Dendritic cells (DCs) are known as major antigen-presenting cells, and lymph nodes (LNs) play an important role in the DC-mediated immune response. This study focused on infiltration of CD1a-positive DCs (CD1a-DCs) in regional LNs in 70 cases of gallbladder cancer (GBC). The results showed that LNs infiltration by CD1a-DCs was associated with unfavorable clinical outcomes in patients with GBC in univariate analyses, but all cases categorized as CD1a-DCs high group at regional LNs had nodal metastasis. Therefore, LNs infiltration by CD1a-DCs was not an independent prognostic factor identified by multivariate analyses. The subgroup analyses in cases with LN metastasis group (n = 32), significant impact of CD1a-DCs infiltration into metastatic LNs was not observed. In contrast, CD1a-DCs infiltration into primary tumor had a significant impact on surgical outcomes. As the results of previous reports that focused on CD1a-DCs infiltration in regional LNs of other organs were varied, the role and significance of CD1a-DCs infiltration in regional LNs may be different according to the tumor histology or primary site. Accumulation of further studies is needed to clarify the role and significance of CD1a-DCs infiltration into regional LNs of solid cancers.

Lymph node invasion in prostate cancer is a significant prognostic factor indicating worse prognosis. While it affects significantly both survival rates and recurrence, proper management remains a heated issue. Thorough evaluation of risk factors associated with nodal involvement, such as lymph node density or extracapsular extension, is crucial to establish potential expansion of the disease and to substratify patients clinically. There are multiple strategies that may be taken into consideration for patients with positive lymph nodes. Nowadays therapeutic methods are generally based on observation, radiotherapy, and androgen deprivation therapy. However current guidelines are incoherent in terms of indication of the most effective management approach. Future management strategies will be expected to reach for novel diagnostic tools and therapies, such as photodynamic therapy or diagnostic imaging with prostate specific membrane antigen. Nevertheless, this heterogeneous group of men remains a vast therapeutic concern, and both clarification of the guidelines and optimal substratification of patients is required.

Dendritic cells (DCs) are the most specialized antigen-presenting cells and lymph nodes (LNs) play an important role in the DC-mediated T-cell response. We evaluated the infiltration of CD1a-positive DCs (CD1a-DCs) i.e. immature DCs, and S100-positive dendritic cells (S100-DCs), a mixture of immature- and mature DCs, in 73 cases of laryngeal cancer and its regional LNs. Among them, 31 patients underwent radiotherapy (RT) or chemoradiotherapy (CRT) prior to surgery. No significant difference was found for CD1a-DC infiltration in the primary tumor, metastatic LNs and non-metastatic LNs, while S100-DCs were significantly fewer in number in the primary tumor and metastatic LNs compared to non-metastatic LNs. Cases which showed a high infiltration of S100-DCs in metastatic LNs appeared to show a favorable prognosis although statistical significance was not reached. In the RT/CRT group, infiltration of CD1a-DCs and S100-DCs were fewer in the primary tumor and metastatic LNs compared to the treatment naive group. Conversely, the RT/CRT group showed higher CD1a-DCs and S100-DCs numbers in non-metastatic LNs compared to the treatment naïve group. Thus, DC maturation in metastatic LNs plays an important role in tumor immunity in laryngeal cancer, and infiltration of DCs into the primary tumor and metastatic LNs is impaired by RT/CRT.

In the surgical treatment of lung cancer, systemic mediastinal lymph node dissection, as one important routine procedure, has been accepted by most peers in the world. However, due to the special location of some mediastinal lymph nodes, the difficulty of dissection, and the negative preoperative CT results, the specific scope of lymph node dissection is still controversial. Especially the second group, which is located at the top of thorax, is likely to be overlooked for the above reasons. Here, we report a case of lung adenocarcinoma in which the preoperative CT showed no abnormal lymph nodes in the second group and also no enlarged lymph nodes of the second group were found during the surgery, yet lymphadenectomy was still performed according the routine with the lymph node of station 2 being sampled. In the postoperative pathological report, cancer cells were found in the second group, instead of lung adenocarcinoma, these cells come from thyroid and were proved to be papillary thyroid carcinoma, which is unusual because no obvious indication of thyroid carcinoma was found in preoperative color doppler ultrasound of superficial lymph nodes.

Unwanted proteins and metabolic waste in cerebral spinal fluid are cleared from the brain by meningeal and nasal lymphatics, and perineural sheath of cranial nerves; however, the distribution and clearance of CSF along the subarachnoid space of the entire spinal cord is not fully understood. It was hypothesized that the anatomical resolution of Cryo-Fluorescence Tomography (CFT) could provide the visual evidence of clearance across the spinal cord at each level of the vertebral column. To that end, isoflurane anesthetized mice were infused into the lateral cerebroventricle with 5.0 µl of quantum dots [QdotR 605 ITKTM amino (PEG)] over two mins. Mice were allowed to recover (ca 2-3 min) and remained awake and ambulatory for 5, 15, 30, 60 and 120 minutes after which they were euthanized, and the entire intact body frozen at -800. The entire mouse was sectioned and imaged to produce an isotropic voxel resolution of 35 µm. Both white light and fluorescent images were captured after each slice to produce high resolution three-dimensional volumes for each mouse. CFT highlighted the circulation of tracer throughout the ventricular system and central canal of the spinal cord and the entire subarachnoid space of the CNS. Signal could be visualized in the nasal cavity, deep cervical lymph nodes, thoracic lymph nodes and more superficial submandibular lymph nodes as early as 15 min post infusion. Fluorescent signal could be visualized along the dorsal root ganglia and down the proximal extension of the spinal nerves of the thoracic and lumbar segments at 30 min. There was significant accumulation of tracer in the lumbar and sacral lymph nodes between 15- 60 min. The dense fluorescent signal in the thoracic vertebrae noted at 5- and 15-mins post infusion was significantly reduced by 30 min. Indeed, all signal in the spinal cord was ostensibly absent by 120 min except for trace amounts in the coccyx. The brain still had some residual signal at 120 min. These data show that Qdots with a hydrodynamic diameter of 16-20 nm rapidly clear from the brain of awake mice. These data also clearly demonstrate the rapid distribution and efflux of trace along a major length of the vertebral column and the potential contribution of the spinal cord in the clearance of brain waste.

Conversational artificial intelligence (AI) has shown strong capabilities in providing low-cost and timely interventions for a wide range of people and increasing well-being. Therefore, this study examined ChatGPT’s efficacy in conducting psychological counseling and its potential for providing accessible psychological interventions, especially in school settings. This study assessed the strengths and limitations of AI to inform future research. Data were generated from ChatGPT’s responses to 80 counseling questions that college students asked during a school counseling setting. All the responses generated during these simulated counseling sessions were then analyzed using three primary metrics—warmth, empathy, and acceptance—following APA guidelines. The analysis adopted several natural language processing methodologies for emotion detection and empathy measurement to quantify ChatGPT’s high efficacy in presenting the appropriate emotions and reactions for counseling. Some responses demonstrated randomness, which is crucial for consideration regarding the use of ChatGPT or relevant technology in psychological counseling. The Discussion section also highlights future directions in the application of conversational AI to enhance students’ mental health.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/ml and/or Gleason score ≥8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes / lymph node metastases outside the established node template in high-risk PCa.

False positives on multiparametric (mp)-MRI result in a large number of unnecessary biopsies in men with clinically insignificant diseases. This study investigates whether quantitative diffusion MRI can improve differentiation between false positives, true positives and normal tis-sue. Twenty-three patients underwent mp-MRI and Vascular, Extracellular and Restricted Diffu-sion for Cytometry in Tumours (VERDICT)-MRI, followed by transperineal biopsy. The patients were categorised into two groups following biopsy: (1) significant cancer - true positive (2) atro-phy/inflammation/high-grade prostatic intraepithelial neoplasia (PIN) - false positive. The clinical apparent diffusion coefficient (ADC) values of the lesions were obtained, and the intravoxel inco-herent motion (IVIM), diffusion kurtosis imaging (DKI) and VERDICT models were fitted using a deep learning approach. Significant differences (p < 0.05) between true positive and false positive lesions were found in ADC, IVIM perfusion fraction (f) and diffusivity (D), DKI diffusivity (DK) and kurtosis (K) and VERDICT intracellular volume fraction (fIC), extracellular-extravascular vol-ume fraction (fEES) and diffusivity (dEES) values. Significant differences between false positives and normal tissue were only found for the VERDICT fIC. These results demonstrate that model-based diffusion MRI could reduce the number of unnecessary biopsies due to false positive prostate lesions and shows promising sensitivity to benign diseases that mimic cancer.

Tackling the intricacies of network dismantling in complex systems poses significant challenges. This task has relevance across various practical domains, yet traditional approaches focus primarily on singular metrics, such as the number of nodes in the Giant Connected Component (GCC) or average pairwise connectivity. In contrast, we propose a unique metric that concurrently targets nodes with the highest degree and reduces the GCC size. Given the NP-hard nature of optimizing this metric, we introduce MaxShot, an innovative end-to-end solution that leverages graph representation learning and reinforcement learning. Through comprehensive evaluations on both synthetic and real-world datasets, our method consistently outperforms leading benchmarks in accuracy and efficiency. These results highlight MaxShot’s potential as a superior approach to address the network dismantling problem effectively.

In this study we discuss critical issues in modelling the structure and function of lymph nodes (LNs), with emphasis on how LN physiology is related to its multi-scale structural organization. In addition to macroscopic domains such as B-cell follicles and the T cell zone, there are vascular networks which play a key role in the delivery of information to the inner parts of the LN, i.e., the conduit and blood microvascular networks. We propose object-oriented computational algorithms to model the 3D geometry of the fibroblastic reticular cell (FRC) network and the microvasculature. Assuming that a conduit cylinder is densely packed with collagen fibers, the computational flow study predicted that the diffusion should be a dominating process in mass transport than convective flow. The geometry models are used to analyze the lymph flow properties through the conduit network in unperturbed- and damaged states of the LN. The analysis predicts that elimination of up to 60–90 % of edges is required to stop the lymph flux. This result suggests a high degree of functional robustness of the network.

Over the past several years there has been much debate with regards to the prognostic and clinical significance of pancreatic ductal adenocarcinoma (PDAC) with lymph nodes metastasis. The PDAC gene-expression knowledge and the biologic alterations underlying the lymph node involvement convey a clinical implication in dealing with the theranostic window.To this end, we provide an original bioinformatic dissection of the gene-expression differences of PDAC according to the nodal involvement from a large public available dataset. Comprehensive transcriptomic analysis from 143 RNA-seq patient’s derived samples indicated that WNT increased activation and a peculiar immune-microenvironment identify subjects with nodal involvement.In frame of this thinking, we validated the WNT pathway role in increasing the likelihood of lymphatic dissemination in vitro. Moreover, we demonstrated for the first time in a PDAC model the potential therapeutic window that XAV-939, a specific WNT pathway inhibitor, has in re-educating a tumour permissive immune system. Finally, we outline the potential implication on bystander molecular drivers exerted by WNT molecular inhibition, providing a picture of the proteomic oncogenic landscape changes elicited by XAV-939 on PDAC cells and their clinical implication. Our findings hold the promise to identify novel immune-based therapeutic strategies targeting WNT to enhance PDAC cytotoxicity and restore anti-PDAC immunity in nodes-positive disease.

Breast cancer remains a significant health concern worldwide, necessitating early detection and treatment. The rapid appearance or a change in the shape of skin lesion on the breast or just of the nipple-areola complex(NAC), especially if it is unilateral needs to be evaluated. Several primary or secondary tumours such as inflammatory skin lesions can affect this body area. Ultrasound, mammography, or magnetic resonance imaging (MRI) are the most used non-invasive diagnostic techniques for breast cancer, but in recent years reflectance confocal microscopy (RCM) and optical coherence tomography have emerged as additional tools to diagnose cases characterized by cutaneous changes.The introduction of new techniques such as reflectance confocal microscopy (RCM), may open new perspectives in the non-invasive diagnosis of mammary paget disease (MPD). RCM is a non-invasive diagnostic technique that allows high-resolution images of the skin at microscopic level in real time. It is non-invasive, painless and repeatable, making it a valuable tool in the early diagnosis and monitoring of skin diseases. We describe an atypical clinical presentation of mammary paget disease early diagnosed by reflectance confocal microscopy evaluation.

(1) Background: Sentinel lymph node (SLN) mapping represents an accurate and feasible technique for the surgical staging of endometrial and cervical cancer. This is commonly performed by conventional laparoscopy or robotic-assisted laparoscopy, but in recent years, a new retroperitoneal transvaginal natural orifice transluminal endoscopic surgery (vNOTES) approach has been described. This technique provides easy visualization of lymphatic afferent vessels and pelvic lymph nodes, early SLNs assessment, and a coherent mapping methodology following the lymphatic flow from caudal to cranial. However, only a few publications have reported it. Following the IDEAL (Idea Development Exploration Assessment Long-term follow-up) framework, research concerning this technique is at stage 2a, with only small case series as evidence of its feasibility. Its standardized description appears necessary to provide the surgical homogeneity required to move further. (2) Methods: description of a standardized approach for retroperitoneal pelvic SLN mapping by vNOTES. (3) Results: we described a 10-step approach to successfully perform retroperitoneal vNOTES SLN mapping, including pre-, intra-, and postoperative management. (4) Conclusions: This IDEAL stage 2a study could help other surgeons approach this new technique, and it proposes a common methodology necessary to evolve through future IDEAL stage 2b (multi-center studies) and stage 3 (randomized controlled trials) studies.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

Background and aims. Clinically significant delayed bleeding (CSDB) may complicate endoscopic colorectal submucosal dissection (ESD). Methods. We assessed the results of a prospective registry of colorectal ESD. We evaluated the effect of clip closure and PuraStat application for prevention of CSDB. Results. 40 patients with 41 colorectal ESD were included. ESD was successful in 38 lesions (92.7%), 35 with R0 resection (92.1%) and 33 with curative resection (86.8%). CSDB occurred in 3 out 38 lesions (7.9%, 95% CI [1.7 – 21.4%]), exclusively after rectal ESD (3 of 22 rectal lesions vs. 0 of 16 colonic lesions, p = 0.249). Clip closure was more frequently used after colonic ESD (12 of 16 colonic lesions vs. 2 of 22 rectal lesions, p < 0.001) and was not protective for CSDB in univariate analysis, even though no events occurred after clip closure (0 of 14 lesions with clip closure vs. 3 of 27 lesions without, p = 0.283). PuraStat was more frequently applied after ESD for rectal lesions (16 of 22 rectal lesions vs. 2 of 16 colonic le-sions, p < 0.001) and was not protective for CSDB, all three events occurring after PuraStat application (3 of 21 lesions with PuraStat application vs. 0 of 20 lesions without, p = 0.097). Conclusions. CSDB occurred exclusively after rectal ESD, and no predictive factors were identified in uni-variate analysis. Clip closure and PuraStat application were not protective for CSDB.

Fibromyalgia (FM) is a chronic central sensitivity syndrome characterized by augmented pain processing at diffuse body sites and presents as a multimorbid clinical condition. Long COVID (LC) is a heterogenous clinical syndrome that affects 10-20% of individuals following COVID-19 infection. FM and LC shares similarities with regards to the pain and other clinical symptoms experienced, thereby posing a challenge for accurate diagnosis. This research explores the feasibility of using surface enhanced Raman spectroscopy (SERS) combined with soft independent modelling of class analogies (SIMCA) to develop classification models differentiating LC and FM. Venous blood samples were collected using two supports, dried bloodspot cards (DBS, n= 48 FM and n= 46 LC) and volumetric absorptive micro sampling tips (VAMS, n= 39 FM and n= 39 LC). A semi-permeable membrane (10 kDa) was used to extract low molecular fraction (LMF) from the blood samples, and Raman spectra was acquired using SERS with gold nanoparticles (AuNPs). Soft Independent Modelling of Class Analogy (SIMCA) models developed with spectral data of blood samples collected in VAMS tips showed superior performance with a validation performance of 100% accuracy, sensitivity, and specificity achieving an excellent classification accuracy of 0.86 area under the curve (AUC). Amide groups, aromatic and acidic amino acids were responsible for the discrimination patterns among FM and LC syndromes, emphasizing the findings from our previous studies. Overall, our results demonstrate the ability of AuNPs SERS to identify unique metabolites that can be potentially used as spectral biomarkers to differentiate FM and LC.

Background: The accurate diagnosis of regional lymph node metastasis is critical for guiding treatment decisions in head and neck cancer patients. Despite advances in imaging techniques, detecting nodal metastasis remains challenging, leading to potential undertreatment or overtreatment. This systematic review aims to identify molecular markers associated with occult metastasis in Head and Neck Squamous Cell Carcinoma (HNSCC) patients. Methods: The present research was conducted following PRISMA guidelines. Prospero registration nr. CRD42024522985. Results: Through a comprehensive literature search and review process, 634 articles were considered, 103 of them were finally included. Conclusions: Several promising markers were identified, including miR-205, DSG3, pan-CK AE1/AE3, HPV-16, Activin-A, Cyclin D1, and NPL that demonstrated effectiveness across multiple studies. Future research should focus on exploring combination scoring systems to improve diagnostic precision and optimize treatment selection in HNSCC patients.

In the present article we describe a few simple and efficient finite volume type schemes on moving grids in one spatial dimension for the sake of simplicity. The underlying finite volume scheme is conservative and it is accurate up to the second order in space. The main novelty consists in the motion of the grid. This new dynamic aspect can be used to resolve better the areas with high solution gradients or any other special features. No interpolation procedure is employed, thus an unnecessary solution smearing is avoided. Thus, our method enjoys excellent conservation properties. The resulting grid is completely redistributed according the choice of the so-called monitor function. Several more or less universal choices of the monitor function are provided. Finally, the performance of the proposed algorithm is illustrated on several examples stemming from the simple linear advection to the simulation of complex shallow water waves. We believe that the techniques described in our paper can be beneficially used to model tsunami wave propagation and run-up.

Genome sequencing is enabling precision medicine—tailoring treatment to the unique constellation of variants in an individual’s genome. The impact of recurrent pathogenic variants is often understood, leaving a long tail of rare genetic variants that are uncharacterized. The problem of uncharacterized rare variation is especially acute when it occurs in genes of known clinical importance with functionally consequent frequent variants and associated mechanisms. Variants of unknown significance (VUS) in these genes are discovered at a rate that outpaces current ability to classify them using databases of previous cases, experimental evaluation, and computational predictors. Clinicians are thus left without guidance about the significance of variants that may have actionable consequences. Computational prediction of the impact of rare genetic variation is increasingly becoming an important capability. In this paper, we review the technical and ethical challenges of interpreting the function of rare variants in two settings: inborn errors of metabolism in newborns, and pharmacogenomics. We propose a framework for a genomic learning healthcare system with an initial focus on early-onset treatable disease in newborns and actionable pharmacogenomics. We argue that (1) a genomic learning healthcare system must allow for continuous collection and assessment of rare variants, (2) emerging machine learning methods will enable algorithms to predict the clinical impact of rare variants on protein function, and (3) ethical considerations must inform the construction and deployment of all rare-variation triage strategies, particularly with respect to health disparities arising from unbalanced ancestry representation.

To assess cognitive impairment and affective symptoms and their association with damage to normal-appearing white matter (NAWM) in patients with clinically isolated syndrome (CIS), we compared neuropsychological test scores between patients with CIS and healthy controls, and examined correlations between these and proton magnetic resonance spectroscopy (1H-MRS) outcomes in patients with CIS. Forty patients with CIS and 40 healthy participants were tested with the set of neuropsychological tests, the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Single-voxel 1H-MRS was performed on frontal and parietal NAWM of patients with CIS to assess ratios of N-acetyl-aspartate (NAA) to creatine (Cr), myo-inositol (mI), and choline (Cho), as well as mI/Cr and Cho/Cr ratios. Patients with CIS had lower cognitive performance, higher scores for the BDI and anxiety subscale of HADS than healthy controls. There were significant correlations between the following neuropsychological tests and metabolic ratios in the frontal NAWM: Stroop Color-Word Test and Cho/Cr, Symbol Digit Modalities Test and mI/Cr as well as NAA/mI, Go/no-go reaction time and NAA/Cho as well as NAA/mI, Californian Verbal Learning Test and NAA/Cr. BDI scores were related to frontal NAA/mI and parietal NAA/Cr and Cho/Cr ratios, whereas HADS-depression scores were associated with frontal NAA/Cr and NAA/mI, and parietal NAA/Cr and Cho/Cr ratios. HADS-anxiety correlated with parietal NAA/Cr ratio. This study suggests that neurochemical changes in the NAWM assessed with single-voxel 1H-MRS are associated with cognitive performance and affective symptoms in patients with CIS.

Bitcoin has been launched for over a decade and made an increasing impact on the world’s financial order, which attracted extensive attention of researchers. Bitcoin system runs on a dynamic P2P network, containing tens of thousands of nodes including reachable nodes and unreachable nodes. In this article, a detection system BNS (Bitcoin Network Sniffer) was prososed, which could collect as many Bitcoin nodes as possible. For reachable nodes, the authors designed an algorithm BRF (Bitcoin Reachable-nodes Finding) based on node activity evaluation, which reduced the nodes to be detected and greatly shortened the detection time. For unreachable nodes, the authors trained a dicision tree model BUF(Bitcoin Unreachable-nodes Finding) to identify unreachable nodes based on attribute features from massive node addresses. Experiments showed that BNS performed better than the website "Bitnodes" in total number and efficiency. Based on the experimental results, the authors analyzed the real network size, node "churn" and geographical distribution.

Yoga promotes acceptance, compassion, physicality, active postures, mental and emotional awareness, and spiritual benefits. It involves breath techniques, postures, and body locks, maintaining balance and strength. It's based on ethical principles. Beyond simple performance, swimming is a catalyst for overall well-being. Complementarily, yoga serves as an invaluable adjunct for swimmers, enhancing flexibility, strength, and body awareness - a triad essential to aquatic excellence. The confluence of yoga and swimming, particularly through the practice of aqua yoga asanas, presents a new paradigm for both athletes and non-performers alike. Athletes who embrace the harmonious fusion of swimming and yoga unearth the potential for achieving not just athletic mastery but also a more balanced and fulfilling lifestyle. This blend provides a route not only to enhance performance in the water but also to elevate the overall quality of life. We examined the feasibility of incorporating yoga and swimming practice into Romanian subjects' lifestyles, designing a factor analysis in SmartPLS software, based on an online survey. The study assesses the participants' knowledge of yoga's theory and philosophy, as well as their perceptions of the swimming practice's benefits for social and health issues. According to our study, Romanian participants practice yoga and swimming as often as possible to reduce stress, improve concentration for work-related tasks, and improve joint elasticity, balance, and muscular tone. Thus, Yoga and swimming are substitutes for other approaches in prevention and therapy.

The increasing emergence of multidrug resistant (MDR) pathogens, due to antibiotics misuse, translates in obstinate infections, with high morbidity and high-cost hospitalizations. To oppose these MDR superbugs, new antimicrobial options are necessary. Although both quaternary ammonium (QASs) and phosphonium salts (QPSs) possess antimicrobial effects, QPSs have been studied at lesser extent. Recently, we have successfully reported on the bacteriostatic and cytotoxic effects of a triphenyl phosphonium salt against MDR isolates of Enterococcus and Staphylococcus genus. Here, aiming at finding new antibacterial devices possibly bactericidal towards a broader spectrum of clinically relevant bacteria, responsible for severe human infections, we synthesized a water-soluble, sterically hindered quaternary phosphonium salt (BPPB). It encompasses two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying the characteristics of molecules known as bola-amphiphiles. BPPB was characterized by ATR-FTIR, NMR and UV spectroscopy, FIA-MS (ESI), elemental analysis and potentiometric titrations. Optical and DLS analyses evidenced BPPB tendency to self-forming spherical vesicles in solution (45 nm by DLS), having a positive zeta potential (+18 mV). The antibacterial effects of BPPB were for the first time assessed against fifty clinical isolates of both Gram-positive and Gram-negative species. Excellent antibacterial effects were observed on all strains tested, involving all the most worrying species included in ESKAPE bacteria. The lowest MICs were 0.250 µg/mL, while the highest ones (32 µg/mL) were observed on MDR Gram-negative metallo-β-lactamase-producing bacteria and/or species resistant also to colistin, carbapenems, cefiderocol, so that intractable with current available antibiotics. Moreover, when administered to HepG2 human hepatic and Cos-7 monkey kidney cell lines, BPPB showed selectivity indices &gt; 10 for all Gram-positive isolated and for clinically relevant Gram-negative superbugs such as those of E. coli species, thus being very promising to be clinically developed.

Biodiversity loss and nature degradation are pressing issues with huge impacts on our society and economy. Businesses, investors, and regulators focus on corporate efforts to support biodiversity and nature positive actions. This review provides a comprehensive overview about the importance of biodiversity in businesses, the materiality of biodiversity and the role of mandatory and non-mandatory regulations on corporate environmental reporting and sustainability disclosure frameworks. The review also discusses descriptive information on the evolution of sustainability frameworks with a comparison of most prominent sustainability frameworks with a key focus on the materiality approach and biodiversity-related disclosure recommendations. Further, we provide suggestions for more holistic approaches to improve the future sustainability frameworks focusing on the biodiversity impact while showing the necessity of more focus on the decision-making paradigm. Further research on measuring biodiversity impact and innovative trends in sustainability reporting are required to better reflect nature-positive outcomes in corporate sector businesses.

Abstract: (1) Background: Sentinel lymph node biopsy assumes importance in the search for metastases, especially in patients with malignant breast disease. Our study approaches the new techniques to prevent complications such as possible postoperative seroma formation, pain or hypoesthesia of the axillary cord and medial arm surface, as well as motor deficits in a preventive manner to avoid disabling outcomes and presents initial data from its experience with the sentinel lymph node biopsy technique. (2) Methods: There are mainly two radioactive tracer detection techniques and a new technique using a radiotracer called Sentimag-magtrace. The positive lymph node is located and removed to perform histologic analysis. In our study, we evaluate 100 patients who underwent breast cancer surgery (3) Results: our experience allowed us to calculate the identification rate with the different methods of sentinel lymph nodes by radioactive tracer 88.9 % vs magnetic tracer technology (Sentimag) 89.5%. (4) Conclusions: Thus, this technique avoids radiation exposure for both patients and health care providers, as well as reducing costs and time.

Gastric cancer is an aggressive disease with increasing global incidence in recent years. Human epidermal growth receptor 2 (HER2) is overexpressed in approximately 10-20% of gastric cancers. The implementation of targeted therapy against HER2 as part of the standard of care treatment in metastatic disease has improved the prognosis of this subset of patients. However, gastric cancer still has high mortality rates and urgently requires new treatment strategies. The combination of immunotherapy with HER2-targeted therapies has shown synergistic effects in preclinical models, being the rationale behind exploring this combination in clinical trials in locally advanced and metastatic settings. Additionally, the irruption of antibody-drug conjugates and other novel HER2-targeted agents has led to the development of numerous clinical trials showing promising results. This review presents the molecular mechanisms supporting the use of HER2-targeted drugs in combination with immunotherapy and provides an overview of the therapeutic scenario of HER2-positive disease. We focus on the role of immunotherapy but also summarize emerging therapies and combinations under clinical research that may change the standard treatment in HER-2 positive disease in the future.

Super-high (x400) magnification dermoscopy (D400) is a new non-invasive imaging technique that has been shown to add information for the differential diagnosis of melanocytic lesions in a pilot study. Our study aimed to confirm if D400 can add details for the discrimination of clinically atypical nevus and melanoma. This is a retrospective observational, multicentric study enrolling patients who received an x20 (D20) and x400 (D400) magnification dermoscopic examination of pigmented skin lesions. Dermoscopic images were retrospectively evaluated by three observers for the presence/absence of nine D20 and twenty D400 dermoscopic features defined in the previous pilot study. Univariate and multivariate analyses were carried out to find predictors of benign and malignant behaviors. At D20 atypical pigment network, blue-whitish veil, atypical vascular pattern, regression, and homogenous pattern were more frequent in melanoma than in nevi (p&lt;0.001). At D400 melanoma showed more frequently than benign lesions melanocytes with an irregular arrangement and irregular in shape and size (p&lt;0.001). Network with edged papillae was more frequent in benign lesions than melanomas (p&lt;0.001). Our study confirms that D400 can identify melanocytes with an irregular arrangement and irregular in shape and size in melanomas, adding information to the conventional D20 examination.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.

AbstractWe investigated the effect of cigarette smoking on pathological staging in clinically low-risk patients. Data of 59 patients who were diagnosed with bladder tumor for the first time and had a single lesion radiologically and endoscopically smaller than 3 cm were investigated retrospectively. 33 patients who smoked were classified as Group I, and 26 patients who did not smoke were classified as Group II. Pathological diagnoses of the patients in both groups were compared. The mean age of the patients were 64.8 (20–86) years. In Group II, 5 (19.2%) were female and 21 (80.8%) were male (p < 0.05). Nine patients (27.3%) in Group I and 18 patients (69.2%) in Group II had Ta disease (p < 0.05). Nineteen patients (57.6%) in Group I and 5 patients (19.2%) in Group II had T₁ disease (p < 0.05). The number of patients with low grade (LG) tumor were 8 (24.2%) and 19 (73.1%) in Group I and in Group II, respectively (p < 0.05). The number of patients with high grade(HG) tumor were 25 (75.8%) and 7 (26.9%) in Group I and in Group II, respectively (p < 0.05). TaHG was detected in 9 (27.3%) patients in Group I. In contrast, no patients in Group II had TaHG disease (p < 0.05). The number of patients with T₁HG was 17(51.5%) patients in Group I and 2 (7.69%) patients in Group II (p < 0.05). Smoking is associated with pathologically HG and stage in patients with first time bladder tumor which is single and smaller than 3 cm.

The complex network is an abstract modeing of complex systems in the real world, which plays an important role in analyzing the function of complex systems. Community detection is an important tool for analyzing network structure. In this paper, we propose a new community detection algorithm (RWBS) based on different seed nodes aims to understand the community structure of the network, which provides a new idea for the allocation of resources in the network. RWBS provides a new centrality metric ($MC$) to calculate node importance, which calculates the ranking of nodes as seed nodes. Furthermore, two algorithms are proposed for determining seed nodes on networks with and without ground-truth, respectively. We set the number of steps for the random walk to 6 according to the six degrees of separation theory to reduce the running time of the algorithm. Since some traditional community detection algorithms may detect smaller communities, e.g., two nodes become one community, this may make the resource allocation unreasonable. Therefore, modularity ($ Q $) is chosen as the optimization function to combine communities, which can improve the quality of detected communities. Final experimental results on real-world and synthetic networks show that the RWBS algorithm can effectively detect communities.

The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.

The needs for environmental reporting to include positive outcomes considering differences between creation of less harm, benefits and net benefits are explored. To become mainstream, nature-positive development needs positive messaging, measures and metrics to guide, plan and assess urban outcomes. With the accelerating climate crisis and negative messages getting the upper-hand, it’s important to avoid paralysis by bad news. Whilst striving for a nature-positive world, more effort should be on moving beyond zero to qualify and quantify benefits, gains, and regenerative outcomes instead of oscillating around damage and loss sticking points. Life Cycle Benefit Assessment (LCBA) is a method to measure gains in accelerating restoration and climate security. It enables a good news focus as its reach is to quantify and show positive gains beyond the negative and zero loss outcomes. The paper aims to clarify concepts, challenges and quantitative methods then review real-world third-party-certified case studies. Climate security, human wellness and resource viability gains inside safe operating space within planetary boundaries are quantified as positive benefits. Contrary to conventional Life Cycle Impact Assessment (LCIA) LCBA assigns damage and loss as negative debts and benefit as positive gains. It concludes that LCBA offers business and design a new environment assessment tool, with research needed on economic and other outcomes.

Multiple preventive vaccines are being developed to counter the COVID-19 pandemic. The leading candidates have now been evaluated in non-human primates (NHPs) and human Phase 1 and/or Phase 2 clinical trials. Several vaccines have already advanced into Phase 3 efficacy trials, while others will do so before the end of 2020. Here, we summarize what is known of the antibody and T-cell immunogenicity of these vaccines in NHPs and humans. To the extent possible, we compare how the vaccines have performed, taking into account the use of different assays to assess immunogenicity and inconsistencies in how the resulting data are presented. We also summarize the outcome of SARS-CoV-2 challenge experiments in immunized macaques, while noting variations in the protocols used, including but not limited to the virus challenge doses.

Our study aimed to identify predictors for the effectiveness of tumor regression in lung cancer patients undergoing neoadjuvant treatment and cancer resections. Patients admitted between 2016 and 2022 were included in the study. Based on the histology of the tumor, patients were categorized into lung adenocarcinoma group (LUAD), and squamous cell carcinoma group (SQCA). Ninety-five patients with non-small cell lung cancer were included in the study. Fifty-eight (61.1%) and 37 (38.9%) patients were included in the LUAD and SQCA groups, respectively. Nine (9.5%), 56 (58.9%), and 30 (31.6%) patients were categorized with a tumor regression score of I, II, and III respectively. In multivariable analyses, histology of the primary tumor (SQCA), lymph node size in the preoperative CT scan (>1.7cm) and absolute tumor size reduction after neoadjuvant treatment (>2.6 cm) independently predict effectiveness of tumor regression (OR, [95% Confidence interval, p-value] of 6.88 [2.40-19.77, p70 years, extended resection >one lobe, and tumor recurrence or metastasis were identified as significant independent predictors of reduced overall survival. Assessment of tumor size before and after neoadjuvant treatment might help to identify high-risk patients with decreased survival and to improve patient management and care.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing in the world population. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems, as well as regulate the expression of multiple genes and, therefore, proteins involved in starvation-satiety processes, activation of brown adipose tissue, increased lipolysis, decreased lipogenesis, and inflammation, beneficial changes in metabolism and improved insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of the bioactive compound.

In rice, symbiotic N fixation via nodule bacteroids does not take place naturally. Although N fixation by endophytic and associative diazotrophs has been reported in rice, main organs and seasonal regulation for the N fixation have not been elucidated. In this study, therefore, seasonal changes of nitrogenase (acetylene reduction) activity and carbohydrate contents in culm internode (IN), basal nodes (BN), and crown root (CR) were investigated in manure compost (MC)- and chemical fertilizer-applied rice. Nitrogenase activity increased after rooting, and reached the highest activity in BN of MC-applied rice at panicle initiation. In BN of MC-applied rice, the sucrose content was low whereas the higher glucose content was detected at panicle initiation. Although bacterial and diazotrophic bacterial populations were most abundant in CR, the nitrogenase activity seemed to be restricted by its trace sucrose and glucose contents. In addition, alpha-Proteobacteria and Clostridia phyla were abundant in BN-specific bacterial microbiota at panicle initiation. These results suggest that the increased N fixation in BN at panicle initiation might be sustained both by the non-structural carbohydrate supply from photosynthetic apparatus and BN-specific bacterial microbiota including diazotrophs.

Lymph nodes are secondary lymphoid organs that appear as bean-like nodules usually <1 cm in size, and they are localized throughout the body. Many antigen-presenting cells such as dendritic cells and macrophages reside in lymph nodes, where they mediate host defense responses against pathogens such as viruses and bacteria. In cancers, antigen-presenting cells induce cytotoxic T lymphocytes (CTLs) to react to cancer cell–derived antigens. Macrophages located in the lymph node sinus are of particular interest in relation to anti-cancer immune responses because many studies using both human specimens and animal models have suggested that lymph node macrophages play a key role in activating anti-cancer CTLs. The regulation of lymph node macrophages therefore represents a potentially promising novel approach in anti-cancer therapy.

Unmanned delivery technology using unmanned aerial vehicles (UAVs) has the potential to solve issues such as traffic congestion and labor shortages. We investigated a method to construct a route between the source and destination nodes in a wireless multi-hop network by installing a radio terminal in each house. If the relay functions of all nodes in the network are in operation, the number of control messages for route construction increases, and the message relay forwarding load of each node increases. Keeping all node pairs multi-hop connectivity, we establish a method to operate the relay function with as few nodes as possible. End nodes that have not activated the relay function connect to the relay node with the closest physical distance. In this paper, we propose methods for selecting nodes to operate the relay function. Specifically, one method is based on random selection, another method is based on the number of adjacent nodes, and a third method is based on the Multipoint Relay (MPR) of the Optimized Link State Routing Protocol (OLSR). For each method, we evaluate whether the route construction is available, the number of relay nodes, the total distance of constructed routes, and the distance in population-dense regions. We clarify the characteristics of each method, and the method based on MPR is the best for constructing a network suitable for UAV navigation routes. In addition, the smaller the number of relay nodes, the more unexpected collisions on the links due to route conflicts. We clarify the minimum node density required to apply the MPR method which reduces the number of relay nodes suppressing route conflicts.

This work focused on the evaluation of some machine learning (ML) models and their application in e-health, using intermediate nodes within an Internet of Things (IoT) platform used for heartbeat anomaly detection. For the evaluation of ML models, a set of statistical validation metrics was selected. These metrics were applied in the training, testing and validation phases of the models. The results obtained can determine relevant factors for the selection of ML models, either based on the statistical and intrinsic efficiency of the ML models, or on their suitability to be implemented in intermediate nodes within an IoT platform. the more Lightweight models such as Simple Linear Regression, Logistic Regression, and K Nearest Neighbors, could easily operate in intermediate nodes, and they are models that require low processing and storage to work. In conclusion, the approach for intermediate nodes of Internet of Things platforms using cognitive networks decreases the processing cost in cloud computing and transfers it to the fog layer.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.

(1) Background: Melanoma is the most aggressive tumor located at the skin level and the man-agement of this pathology requires a correct staging as well as a modern oncological treatment, adapted to each patient. The main objective of the study is to determine the variability of lymphatic drainage in the case of melanomas located on the trunk; (2) Methods: This retrospective study in-cluded 62 cases of melanoma located on the trunk operated between July 2019 and March 2023 in which SLNB was performed and a total of 84 lymph node were excised; (3) Results: Patients had an average age of 54.5 years old, while melanomas had a mean Breslow index of 2.3 mm. The distri-bution of trunk melanomas was: upper trunk 54 cases, lower trunk 30 cases (64.3 % vs. 35.7%). The type of anesthesia chosen was general anesthesia in 53 cases, respectively spinal anesthesia in 9 cases (85.5% vs. 14.5%, p<0.001). The number of sentinel lymph nodes was 54 for melanomas lo-cated on the upper trunk, 8 cervical and 46 axillary, respectively 30 sentinel lymph nodes in cases of melanomas of the lower trunk, 16 at the axillary level and 14 at the inguinal level; (4) Conclusions: Lymph node involvement in melanoma represents an important prognostic factor and the different lymphatic drainage pathways in relation to the location of the primary tumor represents an im-portant objective in the management of this pathology.

JAK2 V617F is a somatic mutation associated with myeloproliferative neoplasm (MPN): polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). In MPNs this mutation is associated with the germline GGCC (46/1) haplotype. Most studies consider the association of the JAK2 haplotypeGGCC_46/1 with some MPNs clinical parameters but no one analyzed the association between JAK2 haplotypeGGCC_46/1 and the onset of onco-drug resistance. Thus, we assessed for JAK2 46/1 haplotype correlation with therapy response in JAK2 V617F positive patients. Patients with MPN, selected by the Hematology Laboratory of “V. Fazzi” Hospital (LE), were analyzed with RLFP-PCR assay with rs10974944 SNP. Most of them had PV (63%) or PMF (61%). Among patients that developed onco-drug resistance, 58% had C/G genotype and only 11% had the G/G allele. No correlation between onco-drug resistance and JAK2 haplotype 46/1 variants emerged. Nevertheless, we observed that G/G allele seems to be related to MPNs evolution to myelofibrosis and to the development of onco-drug resistance clinical parameters (p-value= 0.002449; odd ratio of 3.701209). Thus, although other analyses are required, due to the narrow cardinality of sample, our findings suggest how the G/G allele could be useful for MPNs diagnosis and for the prediction of the disease outcome.

When training deep neural networks tasks, the most popular choices are cross-entropy loss. On the other hand, in general speaking, a decent loss function can take on shapes that are considerably more flexible and ought to be adapted for different activities and datasets. In most of the classification tasks, generally if the true class is not correctly recognized by the network (top1), that class is placed among the five classes with the highest probability (top5). This shows that the network does not necessarily recognize the correct class with a low probability, but a class similar to it (such as 3 vs. 8 in mnist) assigns a higher probability and this causes a mistake in that task. Accordingly, we proposed a loss function deals with the error of class that the neural network incorrectly recognized as correct, in addition to the correct class error. We call our proposed loss as False Positive Loss (FPL), with the intention of viewing and designing loss functions not only through the utilization of true class but also through the utilization of the value of false positive classes. One of the core properties of our proposed loss is full adaptability, which makes False Positive Loss be fully capable of getting reformulated by using other widely used loss functions formulas based on the task or the need of the users. Extensive experimental results demonstrate that our suggested loss function outperforms other well-known losses on a variety of tasks and datasets. As can be observed, the performance of our False Positive Loss is superior to that of the cross-entropy loss when it comes to tasks involving 2D picture classification. We have compared our loss with cross entropy as the most common classification loss function on some models (such as ResNet-18, ResNet-50 and Efficientnet-V2) through classification known as a basic computer vision task. with both random or pre-trained initial weights. As a result, in some cases the models with our loss outperform the same tasks with cross entropy from the viewpoint of some metric (i.e. accuracy and FP). For example, the resnet-50 on cifar-10 dataset with random initialization indicated a top1 accuracy of 94.93 with cross entropy and 95.25 with our loss, while for top5 accuracy the results are 99.86 and 99.87, respectively.

Elevated circulating triglyceride levels have been linked to an increased risk of diabetes, although the precise mechanisms remain unclear. This study aimed to investigate whether low-density lipoprotein (LDL) cholesterol, homeostatic model assessment (HOMA) for insulin resistance, and C-reactive protein served as mediators in this association across a sample of 18,435 US adults. Mediation analysis was conducted using the PROCESS Version 4.3 Macro for SPSS. Simple medi-ation analysis revealed that all three potential mediators played a role in mediating the associa-tion. However, in the parallel mediation analysis, where all three mediators were simultaneously included, HOMA for insulin resistance remained a significant mediator (indirect effect coefficient, 0.47; 95% confidence interval [CI], 0.43—0.52; p < 0.05) after adjusting for all tested confounding factors. Conversely, LDL cholesterol (indirect effect coefficient, -0.13; 95% CI, -0.31—0.05; p > 0.05) and C-reactive protein (indirect effect coefficient, 0.01; 95% CI, -0.003—0.02; p > 0.05) ceased to be significant mediators. HOMA for insulin resistance accounted for 49% of the association between triglycerides and diabetes. In conclusion, HOMA for insulin resistance was the dominant mediator underlying the association between triglycerides and diabetes. Therefore, reducing triglyceride levels may hold promise for improving insulin sensitivity in diabetic patients.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole. Letrozole inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. Letrozole resistance is increasingly being observed, which poses a unique problem for patients. We reanalyzed transcriptomic data comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two genes that significantly differed between these patients; with “PLK1 signaling events” being the most significant signaling pathway. We also identified PRDX4 and E2F8 as the top transcriptional biomarkers for ER+ treatment resistance. Many of the other significant gene products play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified do not have a characterized role in ER+ breast cancer. Our analysis identified a set of genes that warrant further research to elucidate the molecular mechanism of Letrozole resistance in this patient population, as well as novel high-performing biomarkers. We anticipate that these findings could contribute to improved therapeutic outcomes in human patients.

The present study aims to evaluate the antibacterial activity of five commercially available essential oils (EOs): Lavender (LEO), Clove (CEO), Oregano (OEO), Eucalyptus (EEO), and Peppermint (PEO) against the most-known MDR Gram-positive and Gram-negative bacteria - Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) - alone and in various combinations. Gas Chromatography-Mass Spectrometry (GC-MS) analysis established their complex composition. Then, the antibacterial activity was investigated in vitro by diffusimetric antibiogram method, using sterile cellulose discs with Ø 6 mm impregnated with 10 µl of sample and sterile borosilicate glass cylinders loaded with 100 µl of sample; MIC (µg/mL) for each EO was calculated from IZD values (mm) measured after 24 hours. The following EO combinations were evaluated: OEO+CEO, CEO+EEO, CEO+PEO, LEO+EEO, and EEO+PEO. Then, the influence of each dual combination on 3 conventional antibacterial drugs – Neomycin (NEO), Tetracycline (TET), and Bacitracin (BAC) - activity was investigated. The most active EOs against S. aureus and E. coli were LEO and OEO (IZD = 40 mm). They were followed by the CEO and EEO (IZD = 20-27 mm); PEO exhibited the lowest antibacterial activity (IZD = 15-20 mm). EEO alone showed the highest inhibitory activity on P. aeruginosa (IZD = 25-35 mm). It was followed by the CEO, LEO, and EEO (IZD = 7-11 mm), while PEO proved no antibacterial action against it (IZD = 0 mm). Only one synergic action was recorded (OEO+CEO against P. aeruginosa); EEO+PEO revealed partial synergism against S. aureus and CEO+PEO additive behavior against E. coli. Two triple associations with TET showed partial synergism against E. coli, and the other 2 ones (with NEO and TET) evidenced the same behavior against S. aureus; all contained EEO+PEO or CEO+PEO. Most combinations reported indifference. However, numerous cases were of antagonism between constituents included in double and triple combinations, and EOs with the strongest antibacterial activities belong to the highest antagonistic combinations. A consistent statistical analysis supports our results, showing that EOs with moderate antibacterial activities could generate combinations with higher inhibitory effects based on synergistic or additive interactions.

Background: Colorectal cancer (CRC) is prevalent globally, constituting 11.9% of cases in Mexico. Lymph node metastases are established prognostic indicators, with extracapsular lymph node extension (ENE) playing a crucial role in modifying prognosis. While ENE is associated with adverse factors, certain aspects, like lymph node conglomerates, are underexplored. Matted nodes, clusters of lymph nodes infiltrated by cancer cells, are recognized as an independent prognostic factor in other cancers. This study investigates the prognostic implications of lymph node conglomerates, particularly matted nodes, in colon cancer. Methods: A retrospective analy-sis of 502 colon cancer cases (2005–2018) identified 255 with lymph node metastasis. Cases were categorized into two groups: 1) lymph node metastasis alone (n=208), and 2) lymph node metas-tasis with matted nodes (n=47). A comparative survival analysis was performed. Results: Of the 255 patients, 38% had lymph node metastasis. Patients with matted nodes (18.4%) showed an association with higher pN stage and lymphovascular invasion. The 5-year survival rate for pa-tients with matted nodes was 47.7%, compared to 60% without; however, this association demonstrated only a statistical tendency. Multivariate analysis identified clinical stage and ad-juvant chemotherapy use as independent factors contributing to survival. Conclusion: This study underscores matted nodes as potential prognostic indicators in colon cancer, emphasizing their association with higher pN stage and reduced survival. Further research is essential for validat-ing these findings and integrating matted nodes into the broader context of colorectal cancer management.

Adaptive Sliceable-Bandwidth Variable Transceivers (S-BVTs) are key enabler for future optical networks. In particular, those based on Discrete MultiTone (DMT) modulation and Direct Detection (DD) can be considered a flexible solution suitable to address the cost efficiency requirement of optical metro networks. In this paper, we propose to use this cost-effective S-BVT option/implementation in optical metro networks adopting switching nodes based on Semiconductor Optical Amplifier (SOA) technology. Bit loading (BL) and power loading (PL) algorithms are applied to the Digital Signal Processing (DSP) modules, to maximize the performance and/or the capacity as well as enhance the flexibility and adaptability of the system. Our analysis considers switching nodes based on SOAs with and without filtering elements and fiber spans of 25 km. We present the results up to 100 km, with and without SOA-based nodes. Firstly, we analyze the adaptive BVT transmission using the Margin Adaptive (MA) BL/PL algorithm at a fixed bit rate of 28 Gb/s. The possibility of controlling the SOAs current is a key factor to face the transmission impairments due to the fiber and the filtering elements. We also analyze the system considering Rate Adaptive (RA) transmission at a fixed target BER of 3.8·10⁻³, showing that a maximum capacity above 34 Gb/s can be achieved for a single span of 25 km. Although the cascading of filtering elements still constitutes a limiting factor, we show that an improvement of the net bit rate performance can be obtained thanks to the combined use of S-BVT and SOA technology at the switching nodes, resulting in a promising approach for designing future optical metro networks.

Cervical cancer (CC) continues to be a significant global public health concern, even with preventive measures in place. In women with early-stage CC, the status of lymph nodes is of paramount importance, not only for final prognosis but also for determining the best therapeutic strategy. According to main international guidelines, pelvic full lymphadenectomy (PLND) is recommended for lymph node staging. However, in these early stages of CC, Sentinel lymph node biopsy (SLNB) has emerged as a precise technique for evaluating lymph node involvement, improving its morbidity profile. We performed a literature review through PubMed articles about progress on the application of SLNB in women with early-stage CC focusing on the comparison with PET/CT and PLND in terms of oncological outcomes and diagnostic accuracy. While the superiority of SLNB is clear compared to radiologic modalities, it demonstrates no clear oncologic inferiority over PLND, given the higher detection rate of positive lymph nodes and predominance of no lymph node recurrences. However, due to a lack of prospective evidence, particularly concerning long-term oncological safety, SLNB is not the current gold standard. With careful patient selection and adherence to straightforward protocols, a low false negative rate can be ensured. The aim of the ongoing prospective trials is to address these issues.

(1) Background: although current theories of Post-Traumatic Stress Disorder (PTSD) had focused on depressed mood and intrusion, the mechanism through which depression increases the risk of PTSD remains unclear. Research has concentrated on the hyper-active negative valence system (NVS) (e.g., increased fear and threat responses), but a significant role for hypo-active positive valence system (PVS) (e.g., less neural activation towards rewards) was conceivable. (2) Methods: To investigate the implicit processing in a refugee’s sample, ratings of arousal, dominance, and valence for 60 IAPS pictures (positive, neutral, and negative) were collected from 42 individuals with probable PTSD, and 26 trauma-exposed individuals (M age = 28.49 years, SD = ± 7.78). (3) Results: ANOVAs revealed a main group effect (η2p = 0.379) on arousal, dominance, and valence dimensions, and pictures’ categories (η2p = 0.620). Participants with PTSD responded to unpleasant images with enhanced arousal and lower valence ratings compared with individuals without PTSD. Moreover, arousal ratings were negatively correlated with valence (r = - 0.709, p &lt; 0.01). (4) Conclusions: Our findings supported evidence according to which PTSD origins a state of maladaptive hyperarousal and difficulties in regulating emotions. Positive stimuli are considered less pleasant providing evidence for a complementary involvement of NVS and PVS in PTSD development.

Sublobar resection is a standard surgical procedure for small-sized non-small cell lung cancer (NSCLC). However, clinical role of adjuvant chemotherapy for small-sized NSCLC with pathological lymph node (LN) metastasis after sublobar resection is unknown. National Cancer Database was queried for NSCLC patients between 2004 and 2018. Eligibility included sublobar resection with pathological LN metastasis, R0 resection, Charlson comorbidity score = 0, clinical stage T1a-b, and tumor size ≤ 20 mm. Kaplan-Meier method with log-rank test and multivariable Cox proportional hazards analyses were used for assessing survival. Samples were evaluated before and after propensity score matching (PSM) with respect to age, sex, histologic type, and pathological LN status. Of 810 patients who met the eligibility criteria, 567 (70.0%) underwent adjuvant chemotherapy. After PSM, patients with adjuvant chemotherapy had a significantly longer survival than those without (median survival: 64.3 vs. 34.0 months, hazard ratio for death: 0.61, p < 0.0001). Multivariate analyses after PSM showed that younger age (p = 0.0206), female (p = 0.0005), and adjuvant chemotherapy (p < 0.0001) were independent prognostic factors for longer survival. Adjuvant chemotherapy has a prognostic impact in patients with small-sized NSCLC and pathological lymph node metastasis who undergo sublobar resection.

With the rapid development of China's economy, construction industrialization has become the main development trend of China's construction industry, and the convenient, efficient, environmental protection has become the new fashion, therefore the application of prefabricated building is more and more common. Stair serves as the weak link in prefab type building, the connecting node has an important influence on its failure. In this paper, pseudo-static tests are carried out on the joints in different forms of ladder holes to study the mechanical properties of flexible hinge points filled with flexible materials, and the hysteresis curve, skeleton curve and bearing capacity of each specimen are analyzed. The test results show that the flexible hinge can give full play to its flexible characteristics to ease the stress of ladder beam, pin bolt reinforcement and ladder hole, and the bearing capacity of flexible hinge points is moderate, which can not only mitigate the inclined bracing effect under the action of small and medium earthquakes, but also ensure the stair does not fall off under the action of large earthquakes. Through the experiment comparison, the ladder hole adopts node form 2, which can give full play to the advantage of flexible material.

Accurate retroperitoneal lymph node metastasis (LNM) prediction in early-stage testicular germ cell tumours (TGCT) harbours the potential to significantly reduce over- or undertreatment and treatment-related morbidity in this group of young patients as an important survivorship imperative. We investigated the role of computed tomography (CT) radiomics models integrating clinical predictors for the individualized prediction of LNM in early-stage TGCT. Ninety-one patients with surgically proven testicular germ cell tumours and contrast-enhanced CT were included in this retrospective study. Dedicated radiomics software was used to segment 273 retroperitoneal lymph nodes and extract features. After feature selection, radiomics-based machine learning models were developed to predict LN metastasis. The robustness of the procedure was controlled by 10-fold cross-validation. Using multivariable logistic regression modelling, we developed three prediction models: A radiomics-only model, a clinical-only model and a combined radiomics-clinical model. The models' performance was evaluated using the area under the receiver operating characteristic curve (AUC). Finally, decision curve analysis was performed to estimate the clinical usefulness of the predictive model. The radiomics-only model for predicting lymph node metastasis reached a greater discrimination power than the clinical-only model, with an AUC of 0.84 (± 0.17; 95% CI ) vs 0.60 (± 0.22; 95% CI) in our study cohort. The combined model integrating clinical risk factors and selected radiomics features outperformed the clinical-only and the radiomics-only prediction models and showed good discrimination with an area under the curve of 0.94 ( ± 0.10; 95% CI). The decision curve analysis demonstrated the clinical usefulness of our proposed combined model. The presented combined CT-based radiomics-clinical model represents an exciting non-invasive prediction tool for individualized prediction of LN metastasis in testicular germ cell tumours. Multi-centre validation is required to generate high-quality evidence for its clinical application.

Human papillomavirus (HPV) is a well-known cause of cervical cancer, with HIV infection exacerbating the prevalence of high-risk HPV (HR-HPV) and cervical intraepithelial neoplasia (CIN). ART has been shown to reduce the likelihood of developing squamous intraepithelial lesions (SILs) and HR-HPV prevalence, although its impact on invasive cervical cancer remains inconclusive. In a study in Accra, 250 sexually active HIV-positive women exhibited a high HPV prevalence, emphasising the need for regular screening. HPV testing, visual inspection with acetic acid (VIA), and cytology-based tests are primary screening methods, each with specific advantages and limitations. Cervical cancer rates in sub-Saharan Africa are alarmingly high, necessitating targeted vaccination and prevention strategies.

The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit growth or impair survival of bacterial pathogens. Given their large structural and chemical diversity as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin resistant S. aureus (MRSA) and the multi drug-resistant community acquired strain USA300LAC. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 mg/ml), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane associated mechanism of action.

Background A limited lymphadenectomy may make patients with esophageal squamous cell carcinoma (ESCC) at risk for missing occult nodal disease. This study aimed to determine an effective threshold of lymph nodes (LNs) for evaluation of the quality of lymphadenectomy and discuss the impact of adjuvant chemotherapy on pN0 patients. Methods Patients treated surgically for ESCC between 2010 and 2018 in Sichuan Cancer Hospital were included. NPV (Negative Predictive Value) based on a beta-binomial distribution was developed to assess the confidence of node-negative disease. Kaplan-Meier curves were plotted to compare survival differences among groups. Results When patients had >21 LNs examined, the probability of false-negative findings was estimated at <10%, and NPV was estimated at a high level (>86.5%). For patients with LNs removed ≤21, 5-year OS (or DFS) in postoperative chemotherapy group vs that in surgery group was 65.3% vs 54.6%, p = 0.041 (or 59.2% vs 46.6%, p = 0.033). But for patients with >21 LNs, there were no statistical differences (p = 0.683 for OS or p = 0.942 for DFS). Conclusion Only pN0 patients who were at high risk of occult lymph node metastasis (examined LNs ≤21) could benefit from postoperative chemotherapy.

The purpose of this review is to present the current knowledge about the diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). In this review compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients was presented, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines, recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. Currently, the standard treatment of patients with MIBC is radical cystectomy (RC) with bilateral pelvic lymph node dis-section (PLND). The template of PLND and its therapeutic value remain debatable. Moreover, most guidelines recommend neoadjuvant chemotherapy (NAC). However, there is still lack of definitive evidence of the superiority of neoadjuvant chemotherapy over adjuvant chemotherapy. Nevertheless, the curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach with a combination of chemotherapy and RC. Recent studies demonstrate the growing importance of immunotherapy. Special attention should be paid to cN+ BCa patients as the oncological outcomes are significantly worse for this group.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Background: Learning arrangements in health care profession education are increasingly taking place in digital environments. VR in nursing education, as one of the digital elements, is the subject of controversial debate. On the one hand it supports the authenticity of case studies by adding realistic perspectives and information. On the other hand, the costs of developing and maintaining software and hardware hinder long-term implementation. Methods: In this paper, we describe our findings and insights from two different research projects focused on the incorporation of digital tools, particularly virtual reality (VR), into nursing education. Based on the German context, our aim is to promote the adoption of innovative digital methods in nursing education and to offer invaluable experiences from the field. Results: Starting with a brief recapitulation of the projects, we then elucidate the pedagogical strategies for embedding VR-driven scenarios in nursing education. Based on our experiences during the projects we identify various positive aspects, such as change of perspective and simulating acute situations. Key findings: Although potential drawbacks remain, we advocate long-term implementation and specific use of VR at the interface between theory and practice. Nevertheless it is crucial to establish regular evaluation observing the value of digitalisation, especially VR; for nursing education.

TThis paper delves into the extension and characterization of radial positive definite functions into non-integer dimensions. We provide a thorough investigation by employing the Riemann-Liouville fractional integral and fractional Caputo derivatives, enabling a comprehensive understanding of these functions. Additionally, we introduce a secondary characterization based on the Bernstein characterization of completely monotone functions. The practical significance of our study is showcased through an examination of the positivity of the fundamental solution of the space-fractional Bessel diffusion equation, highlighting the real-world applicability of the developed concepts. Through this work, we contribute to the broader understanding of radial positive definite functions and their utility in diverse mathematical and applied contexts.

Positive education is seen as a transformative methodological approach capable of improving the act of teaching and learning and, above all, essential for the development of students' personal skills and competences. However, few studies have been carried out on this subject in the field of lifelong and adult education. This study works with a sample of 399 people over 16 years of age and students of the Universidad Popular de Dos Hermanas in order to show the relationship between the Pygmalion effect and learned helplessness in the process of acquiring knowledge in adulthood. In this way, three tools were used: a questionnaire that showed teachers' perceptions of students' qualities and behaviour and two that provided information on self-concept, self-esteem, personal and social skills and other variables directly related to emotional intelligence and positive education. It shows how exposure to negative operational conditioning factors influences the psychosocial and socio-educational development of students in every possible way, while on the other hand, it indicates the importance of positive education to compensate for this phenomenology by improving the development and growth of those who study and participate in non-formal education. Likewise, the factorial interrelation of both positive and negative conditioning factors and their incidence on learning is shown; the importance of neutralising the negative components and strengthening the positive reinforcement and the role played by the community and education professionals as catalysts and behavioural modulators at any stage of learning and age group for the achievement of the objectives of the student and of education itself in a broad sense

Estrogen exerts its action via estrogen receptors (ERs), including ERα and ERβ, and has effects on immunomodulation during pregnancy. It is known that there is a remodeling in maternal immunology during pregnancy. However, it is not clear if early pregnancy has effects on the expression of ERα and ERβ in the maternal thymus, lymph nodes, spleen, and liver. In this study, these maternal immune organs were harvested at day 16 of the estrous cycle, and at days 13, 16, and 25 of pregnancy. The mRNA and protein expression of ERα and ERβ was analyzed. The results revealed that mRNA and protein expression of both ERα and ERβ was upregulated in the maternal spleen, and expression of ERα and ERβ in the thymus, lymph nodes, and liver was modulated during early pregnancy. In conclusion, early pregnancy modulates the expression of ERα and ERβ in the maternal thymus, lymph nodes, spleen, and liver in a tissue-specific manner, which is related to the regulation of maternal immune function during early pregnancy.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that disproportionally accounts for the majority of breast cancer-related deaths due to the lack of specific targets for effective treatments. In this review, we highlight the complexity of the transforming growth factor-beta family (TGF-β) pathway and discuss how the dysregulation of the TGF-β pathway promotes oncogenic attributes in TNBC which negatively affects patient prognosis. Moreover, we discuss recent findings highlighting TGF-β inhibition as a potent method to target mesenchymal (CD44⁺/CD24^-) and epithelial (ALDH^high) cancer stem cell (CSC) populations. CSCs are associated with tumorigenesis, metastasis, relapse, resistance, and diminished patient prognosis; however, due to differential signal pathway enrichment and plasticity, these populations remain difficult to target and persist as a major barrier barring successful therapy. This review highlights the importance of TGF-β as a driver of chemoresistance, radioresistance and reduced patient prognosis in breast cancer and highlights novel treatment strategies which modulate TGF-β, impede cancer progression and reduce the rate of resistance generation via targeting the CSC populations in TNBC and thus reducing tumorigenicity. Potential TGF-β inhibitors targeting based on clinical trials are summarized for further investigation which may lead to the development of novel therapies to improve TNBC patient prognosis.

Inducible genetically defined mouse models of cancer uniquely facilitate the investigation of early events in cancer progression, however there are valid concerns about the ability of such models to faithfully recapitulate human disease. We developed an inducible mouse model of progressive lung adenocarcinoma (LuAd) that combines sporadic activation of oncogenic KRas^G12D with modest overexpression of c-MYC (KM model). Histological examination revealed a highly reproducible transition from adenoma to locally invasive adenocarcinoma within 6 weeks of oncogene activation. Laser-capture microdissection coupled with RNA-SEQ was employed to determine transcriptional changes associated with tumour progression. Upregulated genes were triaged for relevance to human LuAd using datasets from Oncomine and cBioportal. Selected genes were validated by RNAi screening in human lung cancer cell lines and examined for association with lung cancer patient overall survival using KMplot.com. Depletion of progression-associated genes resulted in pronounced viability and/or cell migration defects in human lung cancer cells. Progression-associated genes moreover exhibited strong associations with overall survival, specifically in human lung adenocarcinoma, but not in squamous cell carcinoma. The KM mouse model faithfully recapitulates key molecular events in human lung cancer and is a useful tool for mechanistic interrogation of LuAd progression.

This study was conducted to examine whether there are quantitative or qualitative differences in the connectome between psychiatric patients and healthy controls and to delineate the connectome features of major depressive disorder (MDD), schizophrenia (SCZ), bipolar disorder (BD) and the severity of these disorders. Toward this end, we have performed effective connectivity analysis of resting state functional MRI data in these three patient groups and healthy controls. We have used spectral Dynamic Causal Modeling (spDCM), and the derived connectome features were further subjected to machine learning. The results outlined a model of 5 connections, which discriminate patients from controls, comprising major nodes of the limbic system (amygdala (AMY), hippocampus (HPC) and anterior cingulate cortex (ACC)), the salience network (anterior insula (AI), fronto-parietal and dorsal attention network (middle frontal gyrus (MFG) corresponding to dorsolateral prefrontal cortex, frontal eye field (FEF)). Notably, the alterations in the self-inhibitory connection of the anterior insula emerged as a feature of both mood disorders and SCZ. Moreover, 4 out of the 5 connectome features that discriminate mental illness from controls are features of mood disorders (both MDD and BD), namely the MFG→FEF, HPC→FEF, AI→AMY, and MFG→AMY connections, whereas one connection is a feature of SCZ, namely the AMY→SPL connectivity. A large part of the variance in the severity of depression (31.6%) and SCZ (40.6%) was explained by connectivity features. In conclusion, dysfunctions in the self-regulation of the salience network may underpin major mental disorders, while other key connectome features shape differences between mood disorders and SCZ, and can be used as potential imaging biomarkers.

Background: The lymph nodes staging system can predict the prognosis of gastric signet ring cell carcinoma (SRCC), but the optimal system for early and advanced SRCC remains unknown. Methods: This study retrospectively analyzed 693 SRCC patients who underwent radical resection in the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital. The predicted performance of three lymph node staging systems, including pN staging, lymph node metastasis rate (LNR), and log odds of positive lymph nodes (LODDS), was compared using the receiver characteristic operating curve (ROC). The kaplan⁃meier method and the log⁃rank test analyze the overall survival of patients. The Cox risk regression model identifies independent risk factors associated with patient outcomes. The nomogram was made by R studio. Results: The 693 SRCC included 165 early SRCC and 528 advanced SRCC. ROC showed that LODDS had better predictive performance than pN and LNR in predicting prognosis regardless of early or advanced SRCC. LODDS can be used to predict the prognosis of early and advanced SRCC and was an independent risk factor associated with patient outcomes (P=0.002, P<0.001). Furthermore, the nomogram constructed by LODDS and clinicopathological features had good predictive performance. Conclusion: LODDS showed a clear prognostic superiority over both pN and LNR in early and advanced SRCC.

The growing of Brain-Computer Interface (BCI) applications is closely related to the increasing accessibility of Electroencephalography (EEG) hardware (EEG headsets), which are noninvasive, portable, wireless and often with open software. However, there is a limited number of BCI software platforms tailored to help inexperienced programmers in the development of BCI applications. Only few of them integrate BCI applications with IoT devices and services. To address these challenges, a model for visual node-based programming has been designed utilizing BrainFlow library within the Node-RED platform, which can be applied to more than 20 biosensors. New Nodes for Node-RED Library within OpenBCI Category (openBCI toolkit for Node-RED) have been developed for design of EEG-Based Brain-Machine Interface and Integration in IoT. The proposed toolkit have been implemented and validated through a case study for controlling a robotic arm by OpenBCI headset. The results from the pilot experiment demonstrated that through concentration levels classified by BrainFlow performance metrics, the control of a TinkerKit Braccio robot arm is possible.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P &lt; 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P&lt;0.01) and CRP was increased (P&lt;0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

This study aimed to analyze the responsiveness of the 5STS test among stroke patients and to estimate the MCIDs for different severity levels of community ambulation and stages of recovery. The 5STS and comparator instruments [gait speed and Functional Ambulatory Category (FAC)] were evaluated at baseline. These measures were repeated at 4 (Stage 1) and 8 weeks (Stage 2), together with the Global Rating of Change (GROC). The MCIDs were calculated with two anchor-based methods using the GROC as the external criterion. Responsiveness to change for the 5STS was estimated analyzing the correlation with changes in the two comparator instruments and their capacity to discriminate improvement. For the 5STS test, while the MCIDs of the limited community ambulators were similar in the two stages (around 3 s), those of the household ambulators decreased from 1.9 s to 0.72 s. Spearman's rho coefficients showed an acceptable correlation between changes in 5STS and changes for both the FAC and gait speed changes in both stages of recovery. Our study revealed that the 5STS is responsive to functional changes in patients with stroke and that their degree of severity and stage of recovery influence the MCID values of the 5STS.

Mental Disorders are an important public health problem. The main of this study was to analyze the prevalence of Mental Disorders and Environmental Quality. Data on the Prevalence of Mental Disorders, Gross Domestic Product, and Median Years of Schooling from 178 countries were used. A positive association was observed and was independent of Gross Domestic Product and Median Years of Schooling.

Medullary thyroid carcinomas (MTCs) are rare thyroid tumors occurring in both sporadic and hereditary forms and whose pathogenesis is related to RET proto-oncogene alterations. MTCs originate from parafollicular cells, which produce calcitonin that represents the biochemical activity of MTC. Total thyroidectomy is the main treatment for MTC and often cures patients with confined diseases. In cases of metastasis, the approach depends on the rate of progression of disease. We report a case of a 54 years old female with a single, incidentally discovered, thyroid nodule of 1 cm, classified as suspicious MTC after a stimulation test with i.v. calcium. After surgery, we examined the nodule using immunohistochemistry, immunofluorescence and electron microscopy. In addition to calcitonin, we found that it expressed intracellular positivity for the RTK receptors ERBB1 and ERBB2. Consistently with MTC features, ultrastructural examination of the tumor displayed heterogeneous spindle-shaped cells containing two groups of secretory granules. Due to the significant correlation found between high ERBB1/ERBB2 levels in MTCs and extrathyroidal growth, the detection of ERBB1 and ERBB2 expression suggests that the two oncoproteins may possibly be involved in tumor proliferative responses and/or differentiation of C-cells. The biological, prognostic and therapeutic significance of these patterns would merits further investigations.

Lymphadenopathy is a common manifestation of both reactive and malignant diseases, and fine needle aspiration (FNA) is an effective and inexpensive screening method. It can prevent unnecessary invasive surgery and excisional biopsy, especially in benign cases. Unfortunately, the lack of universally accepted terminology for reporting results has hindered its widespread support. The Sydney system proposal for lymph node cytopathology categorization and reporting introduced five diagnostic categories to address the lack of universally accepted terminology for reporting results in lymphadenopathy. Our study analyzed 188 lymph node FNC samples from King Abdulaziz University Hospital, Saudi Arabia, examining clinical follow-up data, pathology records, patient information, and final diagnosis from January 2019 to December 2022. Most specimens were from axillary LNs, with 99.5% tissue correlation. The Sydney System Category classification identified 56.9% of cases as malignant, while 26.1% were benign. The final surgical specimen diagnosis revealed a higher percentage of malignant diagnoses, with the highest ROM in malignant/Category V. In conclusion, our study demonstrates that LN-FNAC offers high diagnostic accuracy for LN aspirates, with the Sydney approach potentially aiding risk stratification and achieving consistency in cytologic diagnosis, but further multi-centric research is needed.

The accurate and timely assessment of lymph node involvement is paramount in the management of patients with malignant tumors, owing to its direct correlation with cancer staging, therapeutic strategy formulation, and prognostication. Dual-energy computed tomography (DECT), as a burgeoning imaging modality, has shown promising results in the diagnosis and prediction of preoperative metastatic lymph nodes in recent years. This article aims to explore the application of DECT in identifying metastatic lymph nodes (LNs) across various cancer types, including but not limited to thyroid carcinoma (focusing on papillary thyroid carcinoma), lung cancer, and colorectal cancer. Through this narrative review, we aim to elucidate the clinical relevance and utility of DECT in the detection and predictive assessment of lymph node metastasis in malignant tumors, thereby contributing to the broader academic discourse in oncologic radiology and diagnostic precision.

Considering the age of the dogs, it was expected that elderly animals would have stiffer thyroids than adults. The aim of this study was to evaluate the thyroid glands of healthy dogs using 2D shear wave elastography in order to establish qualitative and quantitative parameters of tissue stiffness in dogs of different age groups. The B-mode ultrasound and elastography findings were correlated with the weight and sex of the patients, allowing a reference range to be established for different groups of dogs. 31 dogs of different breeds, sexes and sizes were evaluated. Animals with clinical signs or ultrasound findings indicative of endocrine disease or thyroid lesions were not included in the study. Using QelaXtoTM 2D software, shear wave velocity data in m/s and color elastograms were evaluated and calculated. A healthy thyroid has a blue color elastogram, indicative of low stiffness, and there was no distinction between adult and elderly dogs, genders or sizes. The reference range for the shear wave velocity of thyroid tissue assessed by 2D shear wave elastography can be between 1.6 and 2.0 m/s with a variation of ±0.889 in adult and elderly dogs.

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

Prostate cancer is a highly heterogeneous disease, and mortality is mainly due to metastases, but the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM) from 43 patients enrolled in clinical trial. We present evidence that while there are some cases of clonally independent primary tumor foci, 87% of primary tumor foci and metastases are descended from a common ancestor. We demonstrate that genes related to oxidative phosphorylation are upregulated in LNM and in African-American patients relative to White patients. We further show that mutations in TP53, FLT4, EYA1, NCOR2, CSMD3, and PCDH15 are enriched in prostate cancer metastases. These findings were validated in a meta-analysis of 3,929 primary tumors and 2,721 metastases and reveal a pattern of molecular alterations underlying the pathology of metastatic prostate cancer. We show that LNM contain multiple subclones that are already present in primary tumor foci. We observed enrichment of mutations in several genes including understudied genes such as EYA1, CSMD3, FLT4, NCOR2, and PCDH15 and find that mutations in EYA1 and CSMD3 are associated with poor outcome in prostate cancer.

(1) Background: Emotional resilience is defined as the capacity of individuals to cultivate positive emotions and effectively navigate through negative emotions in terms of stress or adversity. Recent research has focused on the significant impact of adolescents’ negative emotions, as opposed to positive emotions, on mental health. The examination of positive emotion provides a distinct viewpoint on the relationship between emotional resilience and mental health in adolescents. Consequently, the current research conducted two separate investigations to examine the impact of adolescent emotional resilience on mental health, as well as the mediating influence of positive emotion. (2) Methods: Study 1 comprised a cross-sectional analysis of 3086 Chinese adolescents, while Study 2 involved a longitudinal examination of 266 Chinese adolescents. (3) Results: Results indicated that emotional resilience was associated with enhanced levels of life satisfaction, self-esteem, and overall mental health, while also demonstrating a negative correlation with symptoms of depression and anxiety. Positive emotions were found to have a partial mediating effect on the relationship between emotional resilience and mental health. These results indicate that emotional resilience not only has a direct impact on mental health but also influences mental health indirectly through positive emotions. (4) Conclusions: The findings highlighted the role of emotional resilience in mitigating psychological problems and enhancing mental health in Chinese adolescents. The implications and limitations were discussed.

This work analyzes a new indoor laboratory data set looking at early fire indicators in controlled and realistic experiments representing different incipient fire scenarios. The experiments were performed within the confines of an indoor laboratory setting using multiple distributed sensor nodes on different room positions. Each sensor node collected data of particulate matter (PM), volatile organic compounds (VOC), CO, CO2, H2, UV, air temperature and humidity in terms of a multivariate time series. These data hold immense value for researchers within the machine learning and data science communities who are keen on exploring innovative advanced statistical and machine learning techniques. They serve as a valuable resource for the development of early fire detection systems. The analysis of the collected data was carried out in dependence of the manhattan distance between the fire source and the sensor node. We found that especially larger particles (&gt; 0.5 μm) and VOCs show a significant dependency with respect to the intensity as a function of the manhattan distance to the source. Moreover, we observed differences in the propagation behavior of VOCs, PM, and CO, which are particularly relevant in incipient fire scenarios due to the presence of strand popagation effects.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Up to 25% of early human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients will relapse despite the improvement achieved by the introduction of HER2-targeted therapy. Beyond trastuzumab, other agents approved for early HER2+ BC include the monoclonal antibody pertuzumab, the antibody-drug conjugate (ADC) trastuzumab-emtansine (T-DM1) and the reversible HER2 inhibitor lapatinib. New agents, such as trastuzumab-deruxtecan or tucatinib in combination with capecitabine and trastuzumab, have also shown an improvement in the metastatic setting. Other therapeutic strategies to overcome treatment resistance have been explored in HER2+ BC, mainly in HER2+ that also overexpress estrogen receptors (ER+). One strategy has been to target the cyclin-dependent kinases 4/6 (CDK4/6) as they are downstream of HER2 and many of the cellular pathways associated with resistance to HER2-targeted therapies play a key role in cell cycle and proliferation. Different trials have explored these strategies with encouraging results, but definitive results are needed. In addition, HER2+ BC is known to be more immunogenic than other BC subgroups, with high variability between tumors. Different immunotherapeutic agents have been investigated in this setting, with promising but controversial results obtained to date.

Background: About 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. Methods: This retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. Results: (GU, N=66, 2,3%), Beckwith-Wiedemann spectrum (BWS, N=32, 1,1%), isolated hemihypertrophy (IHH, N=29, 1,0%), Denys-Drash syndrome (DDS, N=24, 0,8%) and WAGR syndrome (N=20, 0,7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24,5 months vs. 39,0 months), had smaller tumors (334,8mL vs. 496,9mL), less often metastasis (8,2% vs. 18%), but more often nephroblastomatosis (12,9% vs. 1,9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (7,7% increase) and favorable in BWS (84,6% reduction). The event-free survival (EFS) of patients with BWS was significantly (p=0,002) worse than in others. Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a serious-global public health issue. A total of 292 E. coli isolates obtained from fecal samples of pigs in Central (n = 103) and Northeastern (n = 189) provinces of Thailand were included in this study. Eighty-six E. coli isolates were phenotypically confirmed to be β-lactamase producers (29.5%) and screened for the presence of β-lactamase genes. The genes in CTX-M family was most frequently found (90.7%). The blaCTX-M-15 gene (59.3%) was predominantly identified CTX-M genotype, followed by blaCTX-M-14 (31.4%) and blaCTX-M-4 (25.6%). The blaTEM-1 gene was prevalent (75.6%). The blaCTX-M-4 and blaCTX-M-14 genes were located on conjugative plasmid. The results highlight healthy pigs as reservoirs of ESBL-producing E. coli carrying ESBL genes that could be horizontally transferred.

The pursuit of sustainable wellbeing is one of the research objectives of positive experience design. Driven by this goal, the purpose of this paper is to provide an impact-centered sustainable positive experience design model. Firstly, the literature review method was used to define the research status and concept of impact-centered sustainable design. Secondly, an impact-centered sustainable positive experience design model was constructed, and relevant formulas for concept generation and concept evaluation were proposed. Thirdly, design verification was conducted through a workshop. Finally, the Technology Acceptance Model (TAM) questionnaire was used to evaluate and discuss the design model. An impact-centered sustainable positive design model was proposed, which includes the important impact dimensions of sensory experience and meaningful experience on users’ quality of life at different levels: healthy living (pleasure index, health behavior), harmonious community (social connectivity, social contribution), and livable environment (living environment, environmental contribution). Based on positive experience related theory, this study takes long-term impacts as the starting point for sustainable positive experience design, which helps designers to generate design concepts from a systematic and long-term perspective.

Positive recurrence for a single-server queueing system is established under generalised intensity conditions of service which does not assume existence of the density distribution function of service but a certain integral type lower bound as a sufficient condition. Positive recurrence implies existence of the invariant distribution and a guaranteed slow convergence to it in the total variation metric.

This study investigated the associations of imageability with fear reactivity. Imageability ratings of four word classes: positive and negative (i) emotional and (ii) propriosensitive, neutral and negative (iii) theoretical and (iv) neutral concrete filler, and fear reactivity scores – degree of fearfulness towards different situations (TF score) and total number of extreme fears and phobias (EF score), were obtained from 171 participants. Correlations between imageability, TF and EF scores were tested to analyze how word categories and their valence were associated with fear reactivity. Imageability ratings were submitted to recursive partitioning. Participants with high TF and EF scores had higher imageability for negative emotional and negative theoretical words. The correlations between imageability of negative emotional words and negative theoretical words for EF score were significant. Males showed stronger correlations for imageability of negative emotional words for EF and TF scores. High imageability for positive emotional words was associated with lower fear reactivity in females. These findings were discussed with regard to negative attentional bias theory of anxiety, influence on emotional systems, and gender-specific coping styles. This study provides insight into cognitive functions involved in mental imagery, semantic competence for mental imagery in relation to fear reactivity, and a potential psycholinguistic instrument assessing fear tendency.

Peptidyl-prolyl cis/trans isomerases (PPIases) are present in a wide variety of microorganisms, including protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Trichomonas vaginalis, Leishmania major, Leishmania donovani, Plasmodium falciparum, Plasmodium vivax, Entamoeba histolytica, and Giardia intestinalis, all of which cause important neglected diseases. PPIases are classified as cyclophilins, FKBPs, or parvulins and play crucial roles in catalyzing the cis-trans isomerization of the peptide bond preceding a proline residue. This activity assists in correct protein folding. However, the biological structure‒function characterization of PPIases from these protozoan parasites is still incomplete. The recombinant production of these enzymes is highly relevant for this ongoing research. In this review, we explore the structural diversity, functions, recombinant production, and activity and inhibition of protozoan PPIases. We also highlight their potential as biotechnological tools for the in vitro refolding of other recombinant proteins from these parasites. These applications are invaluable for the development of diagnostic and therapeutic tools.

Currently, SARS-CoV-2 infection which is the causative agent for COVID-19 disease is a worldwide pandemic with more than 100 million global cases and more than 2.0 million deaths (as of January, 2021). While several vaccines for prevention of COVID-19 have already been registered by the regulatory authorities, the problem is that the substitution rate of this virus is estimated to be one change per 2 weeks, thus mutations could arise that threaten the efficacy of vaccines. Unfortunately, there is no current evidence from random clinical trials to recommend any specific post-exposure treatment for patients with suspected or confirmed COVID-19 disease. Here we propose an innovative superinfection therapeutic (SIT) strategy, which could complement the development of prophylactic vaccines. SIT is based on clinical observations that unrelated harmless viruses might interact in patients infected with pathogenic virus. During SIT, the patient benefits from superinfection with an apathogenic double-stranded RNA (dsRNA) virus such as the infectious bursal disease virus (IBDV), which is a powerful activator of the interferon-dependent antiviral gene program. An attenuated vaccine strain of IBDV was already successfully administered to resolve acute and persistent infections induced by two completely different viruses, the hepatitis B (DNA) and C (RNA) viruses (HBV/HCV). The safety of orally administered acid-resistant IBDV strain R903/78 reverse engineered viral drug candidate was demonstrated in 10 stage IV cancer patients who exhausted all conventional therapy. Following repeated oral administration of the virus up to 10⁹ infectious units (IU)/ dose, only mild flu-like side effects were reported in some patients. Proof-of-principle efficacy was demonstrated in an early COVID-19 patient who was successfully treated with 3x10⁶ IU of an attenuated IBDV vaccine. A small scale dose-finding Phase I safety study is proposed.

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by re-stricted and repetitive behaviors as well as difficulties with social interaction. Nu-merous studies have revealed aberrant lipid mediators and autoimmunity as a recog-nized etiological cause of ASD that is amenable to therapeutic intervention. Methods: In this study, the relationship between the relative cyclooxygenase-2, / pros-taglandin E2 ratio (COX-2/PGE2) as lipid mediator marker and anti-nucleosome au-toantibodies as autoimmunity marker of ASD was investigated using multiple regres-sion and combined receiver operating characteristic (ROC) curve analyses. The study also sought to identify the linear combination of these variables that optimizes the partial area under the ROC curves. There were forty ASD children and forty age- and sex-matched controls included in the current study. Results: Using combined ROC curve analysis, a notable increase in the area under the curve was seen. Additionally, it was reported that the combined markers had improved specificity and sensitivity. Conclusions: This study shows that using a ROC curve analysis to measure the predictive value of specific biomarkers linked to lipid metabolism and autoimmunity in children with ASD should improve our understanding of the etiological mechanism of ASD and how it is related to metabolism. Early diagnosis and intervention may be facilitated by this knowledge.

It was the aim of this study to examine whether the usage of the vaccine COXEVAC® (Ceva Santé Animale) could reduce the consumption of antibiotics in Q-fever-positive dairy farms. Additionally, the effects of other herd-level factors on the consumption of antibiotics were investigated. In this longitudinal cohort study, 36 farms with vaccination and 13 farms without vaccination participated. In all herds, Coxiella burnetii had been directly or indirectly diagnosed. To compare the treatment frequency of antibiotics between the vaccinated group and the non-vaccinated group, the consumption of antibiotics for each farm was collected using the veterinary documents about the application and delivery of antibiotics. To gather detailed information about herd data, nutrition, milking management, housing, and animal health, the farmers were interviewed with the help of a questionnaire. The results suggest that there might be an association between the vaccination against Q fever and a reduced consumption of antibiotics. Neither herd size nor milk yield level influenced the consumption of antibiotics in the study herds. Type of flooring and udder cluster disinfection while milking were associated with a lower and higher therapy frequency, respectively. Further studies are necessary to elucidate the cause-effect relationship between vaccination and the consumption of antibiotics.

Post chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in non-seminomatous germ-cell tumours (NSTGCTs) is a complex procedure. We evaluated whether 3D computed tomography (CT) rendering and their radiomics analysis help predict resectability by junior surgeons. The ambispective analysis was performed between 2016-2021. Prospective group (A) of 30 patients undergoing CT were segmented using 3D slicer software while retrospective group (B) of 30 patients were evaluated with conventional CT (without 3D reconstruction). CatFisher’s exact test showed a p-value of 0.13 for group A and 1.0 for Group B. Difference between proportion test showed a p-value of 0.009149 (IC 0.1-0.63). Proportion of correct classification showed a p-value of 0.645 (IC 0.55-0.87) for A, and 0.275 (IC 0.11-0.43) for Group B. Furthermore, 13 shape features were extracted: elongation, flatness, volume, sphericity, surface area, among others. Performing logistic regression with the entire dataset, n=60, the results were: Accuracy: 0.7, Precision: 0.65. Using n=30 randomly chosen, the best result obtained was Accuracy: 0.73, Precision: 0.83, with a p-value: 0.025 for Fisher's exact test. In conclusion, the results showed a significant difference in the prediction of resectability with conventional CT versus 3D reconstruction by junior surgeon versus experienced surgeon. Radiomics features used to elaborate an artificial intelligence model improve the prediction of resectability. The proposed model could be of great support in a university hospital, allowing to plan the surgery and to anticipate complications.

This paper proposes a product design model for internalising users’ positive experiences through attachment. First, the research commences with a literature review to define the concepts and research status of positive experience design (PED) and product attachment. Subsequently, the design model is constructed, accompanied by relevant formulas for concept generation. Finally, the model’s validity is verified through a workshop, and its effectiveness is evaluated and discussed using the USE questionnaire. This study incorporates the seven factors of product attachment to activate positive states within the user–product relationship and facilitate the cultivation of positive thinking. Grounded in theories of PED and embracing a product attachment perspective, the attachment-driven PED model offers a systematic approach for generating design concepts that are relevant to user experience.

Abstract: The concept of sustainability applied to sports activities means ensuring that the economic benefits brought about by their development are not obtained at the expense of causing ecological damage or interference in local cultural habits. A cable-ski is a nautical ski system whereby a motorboat is substituted by a cable traction system powered by an electric motor. The effect on the quality of the water in those places that can boast cable-ski facilities has been described in cold freshwater lakes. Objective: Our purpose was to study the evolution of water quality in a ten-year period after the installation of a cable-ski facility in a warm, salted, semi-stagnant pond. Material and Method: Review of the data gathered from the routine test carried out by the Laboratory of the Council of Alcúdia from 2010 to 2019 Results: The levels of dissolved oxygen have increased, being significantly higher in the period 2016 – 2019 than in that of 2010 – 2015. The turbidity of the water has also seen a reduction in the second period with respect to the first. Conclusion: It seems that cable-ski improves the quality of water even warm, high-conductivity, semi-stagnant conditions

This study explores the relationship between positive and negative habits and their rewards over time. Using a bibliographic and documentary approach, we analyze how the temporality of rewards influences the formation and maintenance of habits. We developed the "habit chart", which shows that positive habits, such as reading, healthy eating, physical exercise, meditation and personal relationships, offer incremental and lasting rewards. In contrast, negative habits such as sugar consumption, excessive use of social media and a sedentary lifestyle provide immediate gratification followed by a sharp decline. The analysis was based on studies such as those by Warburton et al. (2006), Lally et al. (2010), and Hu (2003) for positive habits, and Malik et al. (2010) and Kross et al. (2013) for negative habits. We conclude that practical strategies, such as financial incentives and creating enabling environments, can make long-term rewards more tangible, promoting the adoption of healthy behaviors. This study reinforces the importance of the temporality of rewards in habit formation and suggests evidence-based interventions to improve quality of life and general well-being.

Positive Health (PH) has been described as a promising transformative innovation to address the challenges of promoting well-being and reducing the burden of disease. The aim of this study is to review the current state of knowledge about PH as introduced by Huber et al. (2016) within the available scientific literature. A rapid review of the literature following the Cochrane Rapid Review recommendations. Three databases were searched (PubMed, Google Scholar, and CINAHL). Data were extracted and synthesized using a narrative approach. A total of 55 articles were included. Initial evaluation studies reveal promising results both at individual and collective levels. However, a need is expressed in several articles for further refinement of the conceptualization of PH and ways to make the effects of the PH approach more measurable. Professionals also expressed a desire for a more informed application and elaboration of the PH method across various settings and populations to enhance its effectiveness in practice. This rapid review highlights the transformative potential of PH in shifting from a disease-focused to a health-oriented paradigm of healthcare. It underscores the need for continued research regarding further development of the concept and its practical method, along with the necessity for methodological innovation.

Bacteremia and fungemia are significant causes of morbidity and mortality which frequently occur as co-infections with viral respiratory infections including SARS-CoV-2. It was aimed to evaluate the microorganisms isolated from blood cultures of SARS-CoV-2 positive and negative patients and investigate their antimicrobial resistance patterns. A retrospective analysis was performed with the total number of 22,944 blood cultures sent to the laboratory between November 2020 and December 2021. Blood cultures were performed on the BD Bactec automated system. Identification was performed using conventional methods, VITEK-2 and MALDI-TOF MS. Antibacterial/antifungal susceptibility tests were performed according to EUCAST/CLSI recommendations. SARS-CoV-2 tests were performed with RT-PCR. It was detected 1,630 culture positivity belonging to 652 patients. Totally 633 of 652 patients were tested for SARS-CoV-2; 118 (18.6%) were positive and 515 (81.3%) were negative. The bacteria and fungi isolated at the high-est rate in SARS-CoV-2 positive patients were methicillin-resistant coagulase negative staphylococci (MR-CoNS) (21.5%), Escherichia coli (12.4%), Klebsiella pneumoniae (12.4%), Candida albicans (1.65%) and Candida glabrata complex (1.65%); while in negative patients, E. coli (21.3%), MR-CoNS (13.5%), K. pneumoniae (12.05%), C. albicans (2.1%), Candida parapsilosis (1.1%) and Candida tropicalis (0.9%). The fact that the most common isolate was MR-CoNS in SARS-CoV-2 positive patients (p = 0.028); the detection of Acinetobacter baumannii was more frequent (p = 0.001) and the isolation of carbapenem-resistant K. pneumoniae was at a higher rate than in SARS-CoV-2 negative patients; also, the increase in multidrug-resistant strains indicate that healthcare-associated infec-tions should not be disregarded while focusing on the outbreak.

Objectives: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and an increased risk of thrombotic events, including ischemic strokes. Methods: We conducted a retrospective analysis of data from consecutive ischemic stroke patients with ET between March 2014 and February 2023. Results: This case series describes the clinical presentation, radiological features, and management of five patients with ET-associated ischemic strokes, all harboring the JAK2 mutation. The diverse radiological findings suggest that both large and small vessel diseases may be influenced by the prothrombotic state induced by ET. A significant elevation in platelet count was observed to correlate with the emergence of new acute infarctions in some cases. Conclusions: The study highlights combined use of antiplatelet and cytoreductive therapy in preventing secondary stroke events in patients with ET and JAK2 mutations. The heterogeneity of stroke patterns in this population necessitates a comprehensive understanding of the underlying pathophysiological mechanisms and tailored therapeutic approaches.

Women have been leading organizations and communities for centuries, but their journeys in leadership have sometimes been challenging. This paper aims to reflect on women's positive and negative experiences in leadership roles and understand the factors contributing to their successes and challenges.To explore these issues, we will draw on various academic literature, including studies on gender and leadership and case studies of women in leadership positions. We will also examine the cultural and social factors that affect women's experiences in leadership, including bias and discrimination, societal expectations, and work-life balance challenges.One key theme from this analysis is the importance of role models and support networks in helping women succeed in leadership roles. Women with access to mentorship, sponsorship, and peer networks are more likely to thrive in their roles and overcome the challenges they may face. However, lacking female role models and mentors can make it difficult for women to advance in their careers and contribute to feelings of isolation and imposter syndrome.Another important theme is the need for organizations and society to address systemic biases and discrimination that prevent women from reaching their full potential. This can include initiatives such as unconscious bias training, flexible work arrangements, and policies that support gender diversity and inclusion.In conclusion, this paper highlights women's positive and negative experiences in leadership roles and emphasizes the need for ongoing efforts to support and empower women in leadership. By addressing the challenges women face and building a culture of inclusion and support, organizations and society can help unlock the full potential of women leaders and create a more equitable and just world.

In real financial market, the delayed market feedback and the delayed effect of government macro-control are inevitable. And both the delay of market feedback and the delay of macro-control effect bring about the mathematical difficulties in studying stabilization and synchronization of the hyper-chaotic financial system. However, employing Lyapunov function method, differential mean value theorem, suitable bounded hypotheses and pulse control technology results in the globally asymptotical stabilization and synchronization criteria. It is the first paper to drive the stabilization and synchronization criteria under the assumptions of the double delays. Finally, numerical examples illuminate the effectiveness of the proposed methods.